A review of the recent advances in antimicrobial coatings for urinary catheters

Abstract

More than 75% of hospital-acquired or nosocomial urinary tract infections are initiated by urinary catheters, which are used during the treatment of 15-25% of hospitalized patients. Among other purposes, urinary catheters are primarily used for draining urine after surgeries and for urinary incontinence. During catheter-associated urinary tract infections, bacteria travel up to the bladder and cause infection. A major cause of catheter-associated urinary tract infection is attributed to the use of non-ideal materials in the fabrication of urinary catheters. Such materials allow for the colonization of microorganisms, leading to bacteriuria and infection, depending on the severity of symptoms. The ideal urinary catheter is made out of materials that are biocompatible, antimicrobial, and antifouling. Although an abundance of research has been conducted over the last forty-five years on the subject, the ideal biomaterial, especially for long-term catheterization of more than a month, has yet to be developed. The aim of this review is to highlight the recent advances (over the past 10years) in developing antimicrobial materials for urinary catheters and to outline future requirements and prospects that guide catheter materials selection and design.

Statement of significance: This review article intends to provide an expansive insight into the various antimicrobial agents currently being researched for urinary catheter coatings. According to CDC, approximately 75% of urinary tract infections are caused by urinary catheters and 15-25% of hospitalized patients undergo catheterization. In addition to these alarming statistics, the increasing cost and health related complications associated with catheter associated UTIs make the research for antimicrobial urinary catheter coatings even more pertinent. This review provides a comprehensive summary of the history, the latest progress in development of the coatings and a brief conjecture on what the future entails for each of the antimicrobial agents discussed.

Keywords: Antifouling coatings; Antimicrobial coatings; Biocides; Catheter-associated urinary tract infections; Urinary catheter coatings; Urinary catheters.

Figure 1

Types of Urinary Catheters: (A) Condom or single use catheter: used only in males for ~1-week period; (B) Intermittent or short term use catheter: used for a few weeks to months; (C) Foley or long term use catheter: used for a few months up to a year.

Figure 2

Flowchart showing the process of encrustation caused by urease producing bacteria: (A) Urease producing bacteria colonize the catheter with the help of biofilms (B) The urease produced by the bacteria breaks down urinary urea to release ammonia (C) The presence of ammonia in urine raises its pH. (D) The alkalinity of urine causes precipitation of salt crystals that are deposited on the catheter and cause blockage.

Figure 3

Biofilm formation process: (A) Free-floating, or planktonic, bacteria come across a surface submerged in the fluid and within minutes become attached. These attached bacteria produce slimy extracellular polymeric substances (EPS) and colonize the surface. (B) EPS production allows the emerging biofilm community to develop a complex, three-dimensional structure that is influenced by a variety of environmental factors. (C) Biofilm communities develop within hours.

Figure 4

Antimicrobial Mechanisms: (A) Exclusion Steric repulsion: Polymers attached to coating surfaces provide physical barriers to proteins, cells and microbes. (B) Electrostatic repulsion: Charges on coatings prevent the attachment of microbes. (C) Low surface energy: Reduction of external microbial adhesion by the use of low energy surfaces. (D) Biocide releasing: These coatings release biocides, such as silver ion and nitric oxide, and kill microbes. (E) Contact-active: These polymer coatings don’t release biocides but kill multi-resistant microbes upon contact.

Figure 5

Silver ions act as biocides with the help of one or more of the above three mechanisms. In the diagram, we see that the cell membrane has been damaged by silver ions. Also, respiration and DNA replication are inhibited because the silver ions damage the integrity of the cellular structure.

Figure 6

A list of the commonly studied antibiotics that have been used as antimicrobial agent in urinary catheter coating studies.

Figure 7

Chemical structure of chlorhexidine

Figure 8

Chemical structure of triclosan (2, 4, 4’ –trichloro- 2’-hydroxydiphenyl ether)

Figure 9

The different mechanisms for antimicrobial activity by antimicrobial peptides

Figure 10

The reproductive cycles of bacteriophage indicating the lytic cycle that destroys the bacterial membrane resulting in the host cell’s death.

Figure 11

Antimicrobial mechanisms of nitric oxide include nitrosation of amines and thiols in the extracellular matrix, lipid peroxidation and tyrosine nitration in the cell wall, and DNA cleavage in the cellular matrix.

Figure 12

Structures of two commonly studied NO donors: S-nitroso-N-acetyl-DL-penicillamine and S-nitrosoglutathione

Figure 13

Zwitterionic mechanism of antifouling: The hydration layer formed by the electrostatic hydrogen bonds between the water molecules and zwitterions prevent the attachment of the extrapolymeric substance (EPS) produced by the microbial cells. The EPS helps the microbes in attaching to the coatings. However, in the case of zwitterionic coatings, the hydration layer prevents this attachment and inhibits antimicrobial attachment to the device.

Figure 14

Structures of some commonly used zwitterionic polymers for antifouling surfaces

Figure 15

A liposome has at least one phospholipid bilayered membrane. It consists of a hydrophobic tail and a hydrophilic tail. Drugs can be inserted within the liposome and delivered into the subject.